Ms. Sabina A. Murphy, M.P.H. 

Cardiosource.  2006; ?2006 American College of Cardiology

Year Presented

2006

Year Published

2006

Description

The goal of the trial was to evaluate treatment with fondaparinux compared with control (unfractionated heparin or placebo) among patients with ST elevation myocardial infarction (MI).

Drugs/Procedures Used

Patients were randomized to either fondaparinux (2.5 mg/day for up to 8 days or hospital discharge; n=6036) or control (n=6056). Patients were classified as Stratum 1, meaning unfractionated heparin (UFH) was not indicated, or Stratum 2, meaning UFH was indicated. Patients in Stratum 1 received fondaparinux or placebo; patients in Stratum 2 received fondaparinux or UFH. In a factorial design, patients were also randomized to an infusion of glucose-insulin-potassium (GIK) or no infusion. This second randomization was discontinued early.

Principal Findings

Median time from symptom onset to randomization was 4.8 hours. Primary PCI was performed in 31% of patients (0.2% of stratum 1 and 53% of stratum 2). Thrombolytic therapy was used in 45% of patients overall (78% of stratum 1 and 16% of stratum 2), with streptokinase the most used thrombolytic (73%). No reperfusion therapy was used in 24% of patients.

The primary endpoint of death or MI at 30 days was lower in the fondaparinux group compared with the control group (9.7% vs 11.2%, hazard ratio [HR] 0.86, p=0.008). Results were similar at 9 days (HR 0.83, p=0.003) and study end (HR 0.88, p=0.008). Among the components of the composite at 30 days, mortality was lower in the fondaparinux group (7.8% vs 8.9%, HR 0.87, p=0.03), and reinfarction trended lower (2.5% vs 3.0%, HR 0.81, p=0.06). The reduction in death or MI at 30 days in the fondaparinux group were driven by stratum 1 (i.e., UFH not indicated), where death or MI occurred in 11.2% of the fondaparinux group vs 14.0% of the control group (HR 0.79, p<0.05) but there was no difference between fondaparinux and control in stratum 2 (i.e., UFH indicated) (8.3% for fondaparinux vs 8.7% for control, HR 0.96, p=NS). Likewise, there was no difference in death or MI at 30 days in patients who were managed with primary PCI (6.1% for fondaparinux vs 5.1% for control). Guiding catheter thrombosis in the primary PCI cohort occurred significantly more frequently with fondaparinux (n=22 vs n=0, p<0.001), as did coronary complications (n=270 vs n=225, p=0.04).

There was no difference in severe bleeding at 9 days by treatment group (1.0% with fondaparinux vs 1.3% with control, p=NS). Intracranial hemorrhage occurred in 0.2% in each group.

Interpretation

Among patients with ST elevation MI, treatment with fondaparinux was associated with a reduction in death or MI at 30 days compared with control, driven by the reduction in patients in whom UFH was not indicated.

The trial design was very complicated. Benefit appeared to be confined to patients in whom UFH was not indicated (i.e. an antithrombin was not administered) (stratum 1), and thus the comparison was between fondaparinux vs placebo, not fondaparinux vs UFH. Additionally, benefit was confined to patients who did not undergo primary PCI. There were increased coronary complications with fondaparinux in the primary PCI cohort, notably guiding catheter thrombosis.

Conditions

Therapies

Study Design

Randomized. Blinded. Factorial.

Patients Enrolled: 12092

Mean Follow-Up: 3-6 months

Mean Patient Age: Mean age 62 years

% Female: 28

Primary Endpoints

Composite of death or reinfarction at 30 days

Secondary Endpoints

Composite of death or reinfarction at 9 days and at final follow-up

Patient Population

STEMI within 24 hours of symptom onset (shortened to 12 hours of symptom onset midway through trial)

Exclusions

Contraindications to anticoagulation, including those at high risk of bleeding, receiving oral anticoagulants, or with creatinine levels >265.2 mg/dL

Related Trials

Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment (ExTRACT-TIMI 25 ) View

OASIS 5 (OASIS 5) View

Related Guidelines

ST-Elevation Myocardial Infarction: Guidelines for the Management of Patients with

Full Text - PDF
Executive Summary
Pocket Guidelines
PDA

Presented by Dr. Salim Yusuf at the March 2006 ACC Annual Scientific Session, Atlanta, GA.

Figure 1. 

Organization for the Assessment of Strategies for Ischemic Syndromes 6 (OASIS-6)

Source: Clinical image provided by the American College of Cardiology Foundation

     

The OASIS-6 Trial Group. Effects of Fondaparinux on Mortality and Reinfarction in Patients With Acute ST-Segment Elevation Myocardial Infarction. The OASIS-6 Randomized Trial. JAMA. 2006;295:epub before print.

Reprint Address

Ms. Sabina A. Murphy, M.P.H., 350 Longwood Ave 1st Fl, Boston, MA 02115. E-mail: smurphy@perfuse.org